Author Affiliations: Departments of Psychology (Ms Nagamatsu and Dr Handy) and Physical Therapy (Mr Hsu and Dr Liu-Ambrose), University of British Columbia, Vancouver, British Columbia, Canada; The Brain Research Centre (Ms Nagamatsu, Drs Handy and Liu-Ambrose, and Mr Hsu) and The Centre for Hip Health and Mobility (Ms Nagamatsu, Mr Hsu, and Dr Liu-Ambrose), Vancouver Coastal Health Research Institute, Vancouver; and University of Illinois at Urbana-Champaign, The Beckman Institute for Advanced Science and Technology, Urbana (Dr Voss).

Cognitive decline is a pressing health care issue. Worldwide, 1 new case of dementia is detected every 7 seconds.1 Mild cognitive impairment—a well-recognized risk factor for dementia2—represents a critical window of opportunity for intervening and altering the trajectory of cognitive decline in seniors.

Exercise is a promising strategy for combating cognitive decline. Both aerobic training (AT) and resistance training (RT) enhance cognitive performance and functional plasticity in healthy, community-dwelling seniors3- 5 and those with mild cognitive impairment.6 However, to our knowledge, no intervention study has compared the efficacy of both types of exercise on cognitive function and functional brain plasticity in seniors with mild cognitive impairment. Understanding this is crucial to using exercise as a strategy for altering the trajectory of cognitive decline in seniors with mild cognitive impairment.

We conducted a proof-of-concept, single-blinded, randomized controlled trial primarily designed to provide preliminary evidence of efficacy of both RT and AT to improve executive cognitive functions—robust predictors of conversion from mild cognitive impairment to Alzheimer disease7—in senior women with probable mild cognitive impairment. Secondarily, we aimed to examine the effect of both types of exercise on associative memory performance, everyday problem solving ability, regional patterns of functional brain plasticity, and physical function.

Methods

The EXCEL (EXercise for Cognition and Everyday Living) study was a 6-month randomized trial. Eighty-six community-dwelling women 70 to 80 years old were randomly allocated to twice-weekly RT (28 women), twice-weekly AT (30 women), or twice-weekly balance and tone (BAT) training (control group) (28 women). Participants were classified as having probable mild cognitive impairment if they had a score lower than 26 out of 30 on the Montreal Cognitive Assessment8 and had subjective memory complaints.

The 60-minute classes were led by certified fitness instructors. For RT, both a Keiser Pressurized Air system and free weights were used.3 Participants performed 2 sets of 6 to 8 repetitions, and loading was increased when sets were completed with proper form. The AT program was an outdoor walking program. The training stimulus started at 40% of a participant's age-specific target heart rate (ie, heart rate reserve [HRR]) and progressed to 70% to 80% of the HRR. The BAT program consisted of stretching, range of motion, balance exercises, and relaxation techniques.3 This group served to control for confounding variables. Participants were questioned about the presence of any adverse effects and were monitored by instructors.

Results

Of the 86 participants, 77 completed the 26-week trial (26 in the RT group, 24 in the AT group, 27 in the BAT group). Twenty-two participants were included in our fMRI analysis (7 in the RT group, 7 in the AT group, and 8 in the BAT group).

The Table shows the baseline characteristics of our sample and change in scores from baseline to trial completion for the primary and secondary outcome measures, excluding fMRI. Compared with the BAT group, the RT group significantly improved performance on the Stroop Test (P = .04) and the associative memory task (P = .03). Compared with the BAT group, RT also led to functional changes in 3 regions of the cortex—the right lingual (P = .03) and occipital-fusiform (P = .02) gyri and the right frontal pole (P = .03)—during the encoding and recall of associations. In addition, there was a significant positive correlation between change in hemodynamic activity in the right lingual gyrus and change in behavioral associative memory performance (r = 0.51; P = .02). The AT group significantly improved general balance and mobility (P = .03) and cardiovascular capacity (P = .04) compared with the BAT group.

While we previously demonstrated that 12 months of twice-weekly RT significantly improved Stroop Test performance in cognitively healthy women 65 to 75 years old,3 our current study found an improvement after only 6 months in women 70 to 80 years old with probable mild cognitive impairment. Thus, the benefits of RT on selective attention/conflict resolution may be more potent among those at greater risk for dementia.

Baker et al6 previously demonstrated that 6 months of AT improved selective attention/conflict resolution and set shifting performance in older women with amnestic mild cognitive impairment. This may be attributed to differences in both the frequency and intensity of AT between the 2 studies. In addition, our study participants were older and had lower baseline Mini-Mental State Examination scores.

We also demonstrated that 6 months of RT twice-weekly significantly improved associative memory performance, co-occurring with positive functional changes in hemodynamic activity in regions involved in the memorization of associations.10 Impaired associative memory is a hallmark of early stages of Alzheimer disease.

Exercise compliance was low, suggesting that we are providing conservative estimates of the efficacy of RT on cognition and functional plasticity. While the AT group had the highest dropout rate, they demonstrated a significant increase in general cardiovascular capacity. Our findings may not generalize to men or to women of other ages.

In conclusion, our study suggests that twice-weekly RT is a promising strategy to alter the trajectory of cognitive decline in seniors with mild cognitive impairment.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Voss and Liu-Ambrose. Acquisition of data: Nagamatsu, Hsu, and Liu-Ambrose. Analysis and interpretation of data: Nagamatsu, Handy, Voss, and Liu-Ambrose. Drafting of the manuscript: Nagamatsu, Handy, and Liu-Ambrose. Critical revision of the manuscript for important intellectual content: Nagamatsu, Handy, Hsu, Voss, and Liu-Ambrose. Statistical analysis: Nagamatsu, Voss, and Liu-Ambrose. Obtained funding: Liu-Ambrose. Administrative, technical, and material support: Nagamatsu, Hsu, Voss, and Liu-Ambrose. Study supervision: Handy and Liu-Ambrose.

Financial Disclosure: None reported.

Funding/Support: The Pacific Alzheimer's Research Foundation provided funding for this study (Dr Liu-Ambrose).

Previous Presentation: Data from this manuscript were presented as a podium presentation at the International Society for Neuroimaging in Psychiatry; September 9, 2011; Heidelberg, Germany.

Additional Information: Ms Nagamatsu is a Michael Smith Foundation for Health Research Senior Graduate trainee and a Natural Sciences and Engineering Research Council of Canada Doctoral trainee. Dr Liu-Ambrose is a Michael Smith Foundation for Health Research Scholar, a Canadian Institutes of Health Research New Investigator, and a Heart and Stroke Foundation of Canada's Henry J. M. Barnett's Scholarship recipient.

Additional Contributions: Alison Chan, BSc, Jennifer C. Davis, PhD, B. Lynn Beattie, MD, and Peter Graf, PhD, made significant contributions to this study. We thank the instructors for their commitment to the participants' health and safety.